A group of investigators is studying osteoprotegerin function in patients with postmenopausal osteoporosis. Using an engineered mouse strain, they develop a chimeric monoclonal antibody that blocks binding of receptor activator of nuclear factor kappa B (RANK) to RANK ligand (RANK-L). The investigators inject this monoclonal antibody into human subjects. Eight weeks later, a bone biopsy is obtained from all subjects. Which of the following is the most likely observed finding?

Question

A group of investigators is studying osteoprotegerin function in patients with postmenopausal osteoporosis.  Using an engineered mouse strain, they develop a chimeric monoclonal antibody that blocks binding of receptor activator of nuclear factor kappa B (RANK) to RANK ligand (RANK-L).  The investigators inject this monoclonal antibody into human subjects.  Eight weeks later, a bone biopsy is obtained from all subjects.  Which of the following is the most likely observed finding?

Quizplus · Accepted Answer

11ec160b_3b67_4e4b_9249_879a6ec7944b_MD0001_00 Interaction between the receptor for activated nuclear factor kappa B (RANK) and its ligand (RANK-L), is critical for the development of mature, multinucleated osteoclasts. This binding is blocked by osteoprotegerin (OPG), which acts as a decoy receptor for RANK-L (preventing it from interacting with RANK). By binding RANK-L, OPG reduces the differentiation and survival of osteoclasts, resulting in decreased bone resorption and increased bone density. Estrogen maintains bone mass in premenopausal women by inducing production of OPG by osteoblasts and stromal cells and decreasing expression of RANK on osteoclast precursors. The loss of OPG at menopause leads to increased osteoclast activity that predisposes to osteoporosis. Denosumab is a monoclonal antibody used in the treatment of postmenopausal osteoporosis. It works similar to OPG in that it binds RANK-L and prevents its interaction with RANK receptor. Denosumab therefore causes decreased osteoclast differentiation and activity (Choice D) as well as decreased bone resorption. (Choices A and C) RANK (receptor) is not present on osteoblasts, and inhibition of binding of RANK-L to RANK does not affect osteoblast activity or bone mineralization. (Choice E) Osteocytes are derived from osteoblasts. Osteocyte survival is regulated by a variety of factors including mechanical stress, local growth factors, and steroid hormone levels. Although osteocytes produce RANK-L, which acts on osteoclasts, osteocyte survival is not dependent on the RANK signaling pathway. Educational objective: The nuclear factor kappa B (RANK)/RANK-ligand (RANK-L) interaction is essential for the formation and differentiation of osteoclasts. Osteoprotegerin (OPG) blocks binding of RANK-L to RANK and reduces formation of mature osteoclasts, leading to decreased bone resorption. Denosumab is a monoclonal antibody used in the treatment of postmenopausal osteoporosis that works in a manner similar to OPG. __________ References: Prevention and treatment of postmenopausal osteoporosis. (http://www.ncbi.nlm.nih.gov/pubmed/24176761)

A Group of Investigators Is Studying Osteoprotegerin Function in Patients